Radiopharmaceuticals can be used for various purposes. Gamma emitting radiopharmaceuticals are typically used for imaging purposes. The gamma radiation is detectable with scintillation cameras There are many different gamma emitting radioisotopes such as, for example, technetium-99 m.
These, although useful for imaging purposes, are not useful for therapeutic purposes. The gamma radiation is so penetrating it does not have any substantial therapeutic applications. For radiopharmaceutical therapeutic applications, beta emitting isotopes are typically used. Beta radiation is less penetrating and deposits more energy in tissue and thus is used to destroy tissue, particularly cancerous tissue. Rhenium is one particularly well known source of beta emissions. Both rhenium-186 and rhenium-188 emit beta radiation as well as gamma radiation making them useful for detection purposes as well as treatment purposes.
The key to any treatment employing a radiopharmaceutical is localization of the radioactive material at the desired site. General application of a dose of beta radiation to the entire body would be more harmful than good. Therefore, it is extremely critical to ensure that a beta emitting radiopharmaceutical localizes at the selected site. To do this, various site specific compounds which are known to localize in particular tissue and organs are bonded to the radioactive beta emitting composition. The formed complex is then injected into the patient The radioactive material is then transported directly to the selected tissue or organ where it hopefully remains for a protracted period of time selectively destroying the diseased area with the emitted beta radiation.
Rhenium in certain respects provides the basis for very valuable and useful radiopharmaceuticals. Its availability in both the form of rhenium-186 and rhenium-188, which have different beta energies and physical half lives, makes it especially useful. Unfortunately, it is difficult to transfer a rhenium center from one ligand environment to another. Such transfers are necessary in formulations of rhenium labelled site specific compositions such as rhenium labelled antibodies and other rhenium labelled chelate compositions.
Rhenium-186 is obtained by neutron bombardment of rhenium-185. It is obtained in low concentrations. Therefore, a high reaction rate of the rhenium to the site specific composition is very critical. Rhenium-188 produced from a tungsten 188/rhenium 188 generator is obtained at especially low concentrations.
Certain reaction parameters such as high temperature can be used which favor transfer of the rhenium to the site specific composition. But unfortunately, most of these transfers require mild conditions which are not favorable to maximizing reaction efficiency. For example, when bonding a rhenium complex to a monoclonal antibody, the reaction conditions must be kept quite mild or otherwise the monoclonal antibody will be denatured.
In order to optimize certain of these transfer reactions from one metal ligand to another, intermediates have been formed. Ligands such as glucoheptonate have been useful with technetium chemistry. Unfortunately, there has been no good intermediate ligand useful to assist in the transfer reaction with rhenium.